The principal objective of this research program is to relate the genetic control of immunoglobulins to their chemical structure, biosynthesis and biological function. To achieve these objectives, we must develop monospecific antibodies to the genetic markers; i.e., the allotypic specificities, of rabbit Ig. By immunochemical analysis of family sera, genetic data will be obtained to evaluate issues of allelism and linkage. Rabbit colonies of defined genotype, homozygous or heterozygous for all known loci will be developed. The allotypic specificities are used as genetic markers for Ig molecules and cells synthesizing them. For the molecules, quantitative gene expression, allelic exclusion, and somatic recombination will be evaluated by quantitative radioprecipitation. Cell surface Ig allotypes, cells secreting Ig allotypes, and cell sorting by allotype will be done with antibody-coated erythrocytes as indicator cells for immunocytoadhesion and hemolytic plaques. Regulation of Ig biosynthesis will be investigated through study of homogeneous antibodies, and allotype suppression, RNA-allotype-conversion, and cell-free-synthesis combined with antigen and mitogen stimulation. The mechanism of allotype-suppression will be investigated in an in vitro model and by sorting B and T cells. Allotype suppression in vivo by zygote transfer will be used to develop animals agammaglobulinemic for selected VH subgroups, Ig classes, or Ig types: a) to obtain large amounts of normally minor populations of Ig; b) to assess the biological requirements for Ig classes or types; c) to assess the limits of the gene pool.